Moderate alcohol consumption has been consistently linked to a lower risk of coronary heart disease (CHD) in observational studies. Short-term trials have shown that alcohol intake has potentially beneficial effects on cardiovascular risk factors, such as HDL-cholesterol, and alcohol inhibits aortic atherosclerosis in several animal models. However, no trial of alcohol intake longer than several weeks has ever been conducted, and the feasibility of a long-term randomized trial on clinical endpoints is uncertain. One approach that could minimize the size and duration of such a randomized trial would be to assess the effect of alcohol on progression of radiologically-defined atherosclerosis, a surrogate outcome with substantial face validity. Such an approach has been shown to give similar results as much larger outcome trials, yet would require fewer participants and a shorter period of observation and have a more favorable risk/benefit balance. Our group recently used this approach to conduct a successful similar pilot study of tea intake. We propose a proof-of-principle pilot study of the effect of longer-term alcohol intake on atherosclerosis. We will recruit and randomize 40 participants aged 55 and older at high risk for CHD to a six-month period of consumption of a single 150 ml glass per day of either 10% ethanol (approximating wine) or water. At baseline and after 6 months, we will assess both aortic and carotid atherosclerosis using magnetic resonance imaging, an accurate and reproducible method for measurement of arterial plaque size and wall volume. We will determine adherence in several ways, including serum markers, dietary recalls, and measurement of unused beverage. The primary outcomes in this feasibility study will be compliance with alcohol intake and the two MRI examinations. As secondary outcomes, we will measure standard and novel cardiovascular risk markers, including inflammatory markers and measures of glucose metabolism. We will assess the effects of alcohol intake on lipoprotein subclass distribution, using NMR spectroscopy, and on serum markers of endothelial function. We will assess safety on a continual basis, including repeated testing of liver enzymes and blood counts, short-form questionnaires, and an independent DSMB. If successful, this pilot study will form the basis for a more definitive trial to determine the effect of alcohol intake on progression of atherosclerosis, which could itself establish the feasibility of even larger, longer- term studies of alcohol intake and occurrence of cardiovascular events. We propose a pilot study to determine the feasibility of a long-term clinical trial of alcohol intake on atherosclerosis, the first step in determining whether moderate drinking prevents cardiovascular disease and hence in understanding the full health effects of alcohol across the population. We will randomize 40 participants aged 55 and older to a six-month period of consumption of 1 glass per day of either pure alcohol (diluted to the strength of wine) or water. At baseline and after 6 months, we will measure several standard and novel cardiovascular risk markers in the blood and will perform magnetic resonance imaging to measure atherosclerosis of the aorta. [unreadable] [unreadable] [unreadable]